DESCRIPTION: Interest in effects of alcohol on blood platelets has grown due to reports that moderate drinking reduces cardiovascular mortality. Alcohol consumption may affect the incidence of disorders involving platelets, including stroke an(f myocardial infarction. Despite the popular view, studies on platelet function have had mixed results. Generally, platelet function is inhibited by alcohol, but other studies show stimulation, particularly of early events in the activation cascade. During withdrawal in alcoholics, platelets undergo a rebound, becoming hypersensitive. Thus a complex, incomplete picture emerges. In particular, few epidemiological studies of how moderate drinking affects platelet reactivity in normal individuals have been performed, and in fact, key preliminary data are still needed before such studies can be effectively proposed. Our hypothesis is that moderate drinking will reduce platelet activity, potentially protecting against thrombosis-related cardiovascular accidents. The long range goal is to conduct a well-controlled epidemiological study of the effects of drinking behavior on platelet function in normal men and women. The goals of the present application are to complete preliminary studies necessary before the performance of such an epidemiological study. Our specific aims are to 1) establish, in normal men and women, the dose-response relationship between alcohol consumption and inhibition of platelet function, including agonist specificity; 2) evaluate time-dependency of responses of platelets to alcohol consumption; 3) determine the most appropriate preparation (whole blood/platelet rich plasma/washed platelets) for measurement of effects of drinking; 4) determine the best-suited mechanistic studies for alcohol's effects on the hemostatic system, for application to later epidemiological studies, including effects on thromboxane production, cyclic nucleotides, and the plasminogen activator system. These studies will address, in a clinically relevant manner, a deficit in our knowledge of how alcohol consumption alters incidence of disease states involving platelets, and lay the groundwork for meaningful epidemiological investigations in this area.